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Four different AAV serotypes (AAV1, AAV2, AAV5, and AAV6) encoding the IL-4 gene were evaluated in rat and human gingival fibroblasts and dental pulp stem cells (DPSCs). AAV2 exhibited the highest transduction efficiency and IL-4 expression in all tested cell types. IL-4 transduced DPSCs demonstrated enhanced osteogenic differentiation, as evidenced by the upregulation of osteogenic markers, increased alkaline phosphatase activity, and elevated calcium deposition. IL-4 transduction activated the extracellular signal-regulated kinase signaling pathway, contributing to osteogenesis. To assess the therapeutic efficacy of AAV2-IL-4 in vivo, a lipopolysaccharide-induced calvarial osteolysis model was established in C57BL\/6 mice. AAV2-IL-4 administration significantly reduced bone resorption, as confirmed by micro-CT and histological analysis. Moreover, IL-4 gene delivery promoted M2 macrophage polarization. These findings highlight AAV2-IL-4 as a promising gene therapy strategy for bone regeneration, effectively integrating immunomodulation and osteogenesis to counteract inflammation-driven bone loss.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziaf060","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T14:36:34Z","timestamp":1745505394000},"source":"Crossref","is-referenced-by-count":3,"title":["Overexpression of interleukin-4 using adeno-associated virus is a potential strategy to enhance bone regeneration"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0558-0281","authenticated-orcid":false,"given":"Hyewon","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Dental Science, Dental Research Institute, School of Dentistry, Seoul National University , Seoul 03080 ,","place":["Republic of 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